The program of gene expression in a cell is controlled by a selected array of transcription factors that are activated in response to extracellular cues. We have cloned and characterized several transcription factors that bind to regulatory regions of the oligodendrocyte myelin genes. One such factor named MYT1 (Myelin transcription Factor 1), a novel member of the zinc finger superfamily, may be instrumental in early stages of oligodendrocyte development and myelin production as well as during regeneration, in each case by coordinating the expression of myelin genes. MYT1 is also expressed in rapidly proliferating, high-grade gliomas, and therefore an examination of MYT1 immunoreactivity may provide additional information to aid in the detection and diagnosis of CNS tumors. Another member of the MYT1 family (named MYT1L) is not expressed in oligodendrocytes, but instead marks neurons at the time they are undergoing their terminal mitosis. The developmental expression and localization of these two multifingered zinc proteins suggests that each may play a role in the development of neurons and oligodendrocytes in the mammalian central nervous system, a possibility that is being investigated via a transgenic mouse strategy. The MYT1 and MYT1L proteins are strikingly upregulated following spinal cord injury, suggesting that both neuronal and glial progenitor cells may have been stimulated to divide or were recruited to the site of injury. Both knockout and dominant negative mutations of MYT1 have been generated. Also, additional proteins that bind to the promoters of myelin genes have been identified in a yeast one-hybrid system, and proteins that interact with MYT1 have been identified with a yeast two-hybrid system. To identify the set of transcription factors that are expressed by oligodendrocytes in response to the individual growth factors that are known to affect the differentiation or survival of oligodendrocytes, we have employed a microarray analysis. One of the growth factors that promotes oligodendroycte differentiation is insulin-like growth factor, IGF-1. In a microarray of 7000 human cDNA clones, we have found that IGF-1 treatment induces the expression of a set of myelin- specific proteins. These studies form the basis for devising strategies to promote remyelination in diseases such as multiple sclerosis, Pelizaeus-Merzbacher disease and spinal cord injury, through the stimulation of oligodendrocyte proliferation and differentiation.